Collagen is the principal structural protein present in vertebrates. Natural collagen is readily available from a variety of domestic animals. The major portion of its structure varies little between mammalian species; and the positions of the distinguishing and structurally significant amino acid residues (glycine, proline, and hydroxyproline), are uniquely consistent in the main helical portion of the collagen.
Purified bovine collagen is used in a variety of medical devices including hemostats, sutures, corneal shields, and soft tissue augmentation. Collagen gels are often intermediates in the preparation of these devices and, in some cases, the gels represent the final medical products.
The term collagen usually implies the collagen present in skin, tendon, and bone. A number of different vertebrate collagens have been identified. All collagens contain a unique triple helix; however, the length of the helix and the nature and size of nonhelical portions of the molecule vary from type to type. The predominant collagen of skin, tendon, and bone is type-I collagen; type-II collagen is essentially unique to cartilage; and type-III collagen occurs in adult skin (5-10%) in association with type I and may be a minor contaminant of type I collagen prepared from this source. The other types occur in small amounts and are usually associated with specific biological structures.
The nonhelical terminal portions of the native collagen molecule, the telopeptides, extend as random coils from the amino and carboxy ends of the molecule. The telopeptide portions of the native collagen are believed to be the major sites of its immunogenicity. Therefore, in order to minimize the immunogenicity of the collagen to be used for the purposes indicated previously and subsequently elaborated upon, it is desirable that the telopeptides be removed. Atelopeptide collagen, or atelocollagen, refers to collagen wherein the telopeptides have been removed.
The term collagen is usually used generically and may apply to the molecule, the native fibril as it exists in situ or is reconstituted in vitro, one of several polymorphic aggregates, or simply to bulk material of unspecified structure. See, Encyclopedia of Polymer Science and Engineering, Vol. 3, 2nd Ed., (John Wiley & Sons, 1985).
Sterile bovine collagen compositions with concentrations up to 10% (w/w) and higher are commercially available. These formulations are prepared by conventional processes whereby collagen is precipitated from the solution and aseptically concentrated. A concentration/separation technique commonly employed in protein recovery is aseptic centrifugation, but this process can require high capital expenditure; moreover, centrifugation presents sterilization and validation challenges and may have product recovery problems, especially for viscous or adhesive materials. Other separation techniques have also been found to be unsatisfactory or difficult to operate in an aseptic manner. For example, dead end filtration and tangential flow filtration are not feasible because collagen tends to clog or blind the filters. Technical problems associated with concentrating collagen are attributable, in part, to the viscosity, adhesiveness and cohesiveness of aqueous collagen dispersions at relatively high concentrations (e.g., above about 2 to 3% w/w).